Evaluation of Calcineurin-inhibitor Reduction With Conver... | NCT01935128

Name	Class
Novartis Pharmaceuticals	INDUSTRY

Label	Type	Description	Intervention Names
Arm 1 Everolimus/Reduced dose tacrolimus	Experimental	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml.	Drug: Arm 1 Everolimus/Reduced dose tacrolimus

Name	Type	Description	Arm Group Labels	Other Names
Arm 1 Everolimus/Reduced dose tacrolimus	Drug	Immunosuppression drug intervention	Arm 1 Everolimus/Reduced dose tacrolimus

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Renal Function	Renal function in patients will be assessed using glomerular filtration rate (GFR) as measured by the Modified Diet Renal Disease (MDRD) estimation. Glomerular filtration is the process by which the kidneys filter the blood, removing excess wastes and fluids. Glomerular filtration rate (GFR) is a calculation that determines how well the blood is filtered by the kidneys, which is one way to measure remaining kidney function. GFR is also used to find the stage of chronic kidney disease. Glomerular filtration rate is usually calculated using a mathematical formula that compares a person's size, age, sex, and race to serum creatinine levels. The higher the GFR number, the better the kidney function; the lower the GFR number, the worse the kidney function. A GFR of 60 or higher is in the normal range. A GFR below 60 may mean kidney disease. A GFR of 15 or lower may mean kidney failure.	2 years
Graft Survival	Graft survival is defined as the percentage of kidney transplants still functioning at 2 years post baseline visit . One patient died of natural causes at 12 months with a functioning graft.	2 years
Biopsy Proven Acute Rejection	The percentage of patients with a treated biopsy-proven acute rejection (a co-primary endpoint) within the 2 year study time period	2 years
Patient Survival	Patient survival is defined as the percentage of patients still surviving at 2 years post baseline visit	2 years

Secondary Outcomes

Measure	Description	Time Frame
Impaired Glucose Tolerance	The number of patients with impaired glucose tolerance as indicated by fasting blood glucose levels, Hemoglobin A1C (HgbA1C) levels and the need for hypoglycemic medications	2 years
Proteinuria

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female renal allograft recipients at least 18 years old.
Patients who have given written informed consent to participate in the study. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.
Patient who has received a kidney transplant from a deceased or living unrelated-/related donor.
Recipient of a kidney allograft with a cold ischemia time (CIT) < 36 hours.
Female patients must have a negative pregnancy test prior to study enrollment.
Patients on calcineurin inhibitor(s) (CNI) (tacrolimus and myfortic®) without steroid maintenance following Campath® induction.
Patients with an acceptable allograft function defined by a serum creatinine < 2.5 mg/dL (250 μmol/L) and an actual estimated glomerular filtration rate (eGFR) (Modification of diet in renal disease equation 4, MDRD4) ≥ 30 mL/min/1.73m2 (without renal replacement therapy).
No evidence of rejection since the time of transplantation.

Exclusion Criteria:

Recipient of ABO incompatible allograft or a positive cross-match.
Patient who is human immunodeficiency virus (HIV) positive.
Patient who received an allograft from a Hepatitis B surface Antigen (HBsAg) or a Hepatitis C Virus (HCV) positive donor.
HBsAg and/or a HCV positive patient with evidence of elevated liver function tests (LFTs) (Alanine transaminase/Aspartate transaminase [ALT/AST] levels ≥ 2.5 times upper limit of normal [ULN]). Viral serology results obtained within 6 months prior to randomization are acceptable.
Patient with severe restrictive (total lung capacity [TLC] < 50%) or obstructive pulmonary (forced expiratory volume in one second [FEV1] < 50) disorders.
Patient with severe allergy requiring acute (within 4 weeks of baseline) or chronic treatment that would prevent patient from potential exposure to everolimus, or with hypersensitivity to drugs similar to everolimus (e.g. macrolides).
Patients with a known hypersensitivity/contraindication to any of the immunosuppressants or their classes, or to any of the excipients.
Patient with severe hypercholesterolemia (> 300 mg/dL) or hypertriglyceridemia (> 400 mg/dL) that cannot be controlled despite lipid lowering therapy.
Patient with white blood cell (WBC) count ≤ 1,000 /mm3 (and absolute neutrophil count [ANC] of <500) or a platelet count ≤ 50,000 /mm3.
History of malignancy of any organ system, treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. (Localized basal cell carcinoma of the skin at any time, or small (less than 4 cm) or low-grade renal cancers, bladder cancers, or treated prostate cancer with no evidence of disease after 2 years are allowable)
Graft loss.
Patient on renal replacement therapy.
Patient who experienced biopsy proven rejection.
Proteinuria > 1 g/day (as calculated from the urinary protein-to-creatinine ratio).
Patients with recurrence of Focal Segmental Glomerulosclerosis (FSGS).
Patient who has a current severe systemic infection according to the investigator judgment requiring continued therapy that would interfere with the objectives of the study.
Patients with ongoing wound healing problems, clinically significant infection requiring continued therapy or other severe surgical complication in the opinion of the investigator.
Presence of intractable immunosuppressant complications or side effects.
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum human chorionic gonadotrophin laboratory test (>5 mIU/mL)
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using two birth control methods.

Name	Affiliation	Role
Michael Rees, MD, PhD	University of Toledo, HSC	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Toledo, Health Science Campus		Toledo	Ohio	43614	United States

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Feb 5, 2018

ID	Title	Description
BG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants	BG00050

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Renal Function

Renal function in patients will be assessed using glomerular filtration rate (GFR) as measured by the Modified Diet Renal Disease (MDRD) estimation.

Glomerular filtration is the process by which the kidneys filter the blood, removing excess wastes and fluids. Glomerular filtration rate (GFR) is a calculation that determines how well the blood is filtered by the kidneys, which is one way to measure remaining kidney function. GFR is also used to find the stage of chronic kidney disease. Glomerular filtration rate is usually calculated using a mathematical formula that compares a person's size, age, sex, and race to serum creatinine levels. The higher the GFR number, the better the kidney function; the lower the GFR number, the worse the kidney function. A GFR of 60 or higher is in the normal range. A GFR below 60 may mean kidney disease. A GFR of 15 or lower may mean kidney failure.

Intent to treat population (all participants assigned to treatment arm). Last observation carried forward (LOCF) imputation method

Posted

Mean

Standard Deviation

mL/min/1.73 m2

2 years

ID	Title	Description
OG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants	OG00050

Title

Denominators

Categories

Title	Measurements
	OG00065.70± 20.04

Primary

Graft Survival

Graft survival is defined as the percentage of kidney transplants still functioning at 2 years post baseline visit . One patient died of natural causes at 12 months with a functioning graft.

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants	OG000

Primary

Biopsy Proven Acute Rejection

The percentage of patients with a treated biopsy-proven acute rejection (a co-primary endpoint) within the 2 year study time period

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants	OG000

Primary

Patient Survival

Patient survival is defined as the percentage of patients still surviving at 2 years post baseline visit

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants	OG000

Secondary

Impaired Glucose Tolerance

The number of patients with impaired glucose tolerance as indicated by fasting blood glucose levels, Hemoglobin A1C (HgbA1C) levels and the need for hypoglycemic medications

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants	OG000

Secondary

Proteinuria

The number of patients with proteinuria as defined by spot urine protein to creatinine ratio greater than 1.0

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants	OG000

Secondary

Lipid Levels

The number of patients with hyperlipidemia as defined by the development of new onset hyperlipidemia in the baseline negative patients and the number of baseline positive patients who required starting a new lipid-lowering medication or an increase in dose of their lipid-lowering medication over the course of the study

The overall number of participants analyzed was 50. This population was split into participants who were negative for hyperlipidemia at baseline and developed new onset hyperlipidemia (10) identified in Row 1 and participants who were baseline positive for hyperlipidemia but who required a new lipid-lowering medication or an increase in the dose of their lipid-lowering medication over the course of the study (40) as identified in Row 2.

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants

Secondary

Mouth Ulcers

The number of patients with stomatitis/aphthous ulcer

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants	OG00050

Secondary

Gastrointestinal Complaints

The number of patients with gastrointestinal complaints as indicated by abdominal pain, nausea, vomiting or diarrhea not accounted for by a specific episode of illness such as gastroenteritis

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants	OG000

Secondary

Leukopenia

The number of patients with leukopenia as indicated by white blood cell count less than 1.0, absolute neutrophil count less than 500 or the need for exogenous granulocyte stimulating factor administration

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants	OG000

Secondary

Thrombocytopenia

The number of patients with thrombocytopenia as defined by platelet count less than 50

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants	OG000

Secondary

Neurotoxicity

The number of patients with neurotoxicity as evidenced by incidence of new onset seizure activity or tremors

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants	OG000

Secondary

Pneumonitis

The number of patients with pneumonitis as demonstrated by lung inflammation symptoms such as shortness of breath and/or cough requiring clinical intervention and management

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants	OG000

Secondary

Cytomegalovirus

The number of patients with Incidence of cytomegalovirus infection as defined by need for hospitalization

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants	OG000

Secondary

Infection Requiring Hospitalization

The number of patients with serious infections as defined by need for hospitalization

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants	OG000

Secondary

BK Infection

The number of patients with BK infection as defined by blood titers requiring reduction in immunosuppressive dose

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants	OG000

Secondary

BK Nephropathy

The number of patients with BK nephropathy as defined by biopsy. Note that biopsies were not required as part of the study but were only done as part of the patient's standard of care if rejection was suspected (i.e. if the serum creatinine increased by 25% and was not associated with elevated tacrolimus levels or clinical signs of dehydration/illness to account for elevated creatinine)

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants	OG000

Secondary

Malignancies

The number of patients developing malignancies including post-transplant lymphoproliferative disorders

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants	OG000

Secondary

Cardiovascular Complications

The number of patients with cardiovascular complications as indicated by conditions such as dysrhythmias, coronary artery disease requiring intervention or myocardial infarction

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants	OG000

Secondary

Development of Donor Specific Antibody

The number of patients with incidence of development of donor specific antibody

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Arm 1 Everolimus/Reduced Dose Tacrolimus	In this arm, the myfortic® will be weaned off quickly and everolimus (Zortress®) initiated to achieve a target level of 3-8 ng/ml with a mean of 6 ng/ml. Once achieving a therapeutic dose of everolimus (Zortress®) the tacrolimus (Prograf® or Hecoria®) dose will be reduced a target level of 3-5 ng/ml. Arm 1 Everolimus/Reduced dose tacrolimus: Immunosuppression drug intervention

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Venous thrombosis	Vascular disorders	medDRA	Systematic Assessment	Lower extremity deep venous thrombosis	EG0004 events4 affected50 at risk
Pyrexia	General disorders	medDRA	Systematic Assessment	Fever	EG0005 events4 affected50 at risk
Influenza A	Infections and infestations	medDRA	Systematic Assessment		EG0001 events1 affected50 at risk
Gastroenteritis	Infections and infestations	medDRA	Systematic Assessment		EG0001 events1 affected50 at risk
Rectal hemorrhage	Gastrointestinal disorders	medDRA	Systematic Assessment		EG0002 events1 affected50 at risk
Endocarditis	Infections and infestations	medDRA	Systematic Assessment	Aortic endocarditis	EG0001 events1 affected50 at risk
Diabetes mellitus	Metabolism and nutrition disorders	medDRA	Systematic Assessment		EG0001 events1 affected50 at risk
Urosepsis	Infections and infestations	medDRA	Systematic Assessment	UTI - Organism: Escherichia coli	EG0001 events1 affected50 at risk
Urinary tract infection	Infections and infestations	medDRA	Systematic Assessment	Escherichia coli UTI	EG0001 events1 affected50 at risk
Acute kidney injury	Renal and urinary disorders	medDRA	Systematic Assessment	Increased serum creatinine	EG0001 events1 affected50 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	medDRA	Systematic Assessment	Shortness of breath	EG0003 events3 affected50 at risk
Depression suicidal	Psychiatric disorders	medDRA	Systematic Assessment	Depression - suicidal ideation	EG0001 events1 affected50 at risk
Vascular pseudoaneurysm	Injury, poisoning and procedural complications	medDRA	Systematic Assessment	Left arm arteriovenous fistula pseudoaneurysm	EG0001 events1 affected50 at risk
Kidney transplant rejection	Immune system disorders	medDRA	Systematic Assessment	Donor specific antibody development (kidney rejection)	EG0001 events1 affected50 at risk
Nasal abscess	Infections and infestations	medDRA	Systematic Assessment	Left nostril abscess with facial cellulitis	EG0001 events1 affected50 at risk
Parathyroid gland excision	Surgical and medical procedures	medDRA	Systematic Assessment	Subtotal parathyroidectomy classified as serious adverse event due to hospitalization over 24 hours	EG0001 events1 affected50 at risk
Nephrectomy	Surgical and medical procedures	medDRA	Systematic Assessment	Bilateral native nephrectomy classified as serious adverse event due to hospitalization over 24 hours	EG0002 events2 affected50 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Upper respiratory tract infection	Infections and infestations	medDRA	Systematic Assessment		EG00052 events31 affected50 at risk
Urinary tract infection	Infections and infestations	medDRA	Systematic Assessment		EG00019 events9 affected50 at risk
Fungal skin infection	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment		EG0005 events4 affected50 at risk
Hyperlipidemia	Metabolism and nutrition disorders	medDRA	Systematic Assessment		EG00014 events14 affected50 at risk
Worsening hyperlipidemia	Metabolism and nutrition disorders	medDRA	Systematic Assessment		EG00020 events18 affected50 at risk
Nausea	Gastrointestinal disorders	medDRA	Systematic Assessment		EG0009 events9 affected50 at risk
Vomiting	Gastrointestinal disorders	medDRA	Systematic Assessment		EG0008 events8 affected50 at risk
Diarrhea	Gastrointestinal disorders	medDRA	Systematic Assessment		EG00025 events18 affected50 at risk
Abdominal pain	Gastrointestinal disorders	medDRA	Systematic Assessment		EG0008 events8 affected50 at risk
Abdominal distention	Gastrointestinal disorders	medDRA	Systematic Assessment		EG0003 events3 affected50 at risk
Stomach upset	Gastrointestinal disorders	medDRA	Systematic Assessment		EG0007 events7 affected50 at risk
Gastroenteritis	Gastrointestinal disorders	medDRA	Systematic Assessment		EG0003 events3 affected50 at risk
Weight gain	Investigations	medDRA	Systematic Assessment	> 10 lbs	EG00033 events25 affected50 at risk
Weight loss	Investigations	medDRA	Systematic Assessment	> 10 lbs	EG00012 events11 affected50 at risk
Herpes zoster	Infections and infestations	medDRA	Systematic Assessment		EG0005 events5 affected50 at risk
Hepatic enzyme increased	Hepatobiliary disorders	medDRA	Systematic Assessment		EG00014 events13 affected50 at risk
Stomatitis	Gastrointestinal disorders	medDRA	Systematic Assessment	aphthous mouth ulcers	EG00018 events14 affected50 at risk
Diabetes mellitus	Metabolism and nutrition disorders	medDRA	Systematic Assessment		EG0003 events3 affected50 at risk
Worsening diabetes mellitus	Metabolism and nutrition disorders	medDRA	Systematic Assessment		EG0004 events4 affected50 at risk
Cough	Respiratory, thoracic and mediastinal disorders	medDRA	Systematic Assessment		EG00016 events14 affected50 at risk
Cellulitis	Infections and infestations	medDRA	Systematic Assessment		EG0003 events3 affected50 at risk
Rash, acneiform	Skin and subcutaneous tissue disorders	medDRA	Systematic Assessment		EG0008 events7 affected50 at risk
Worsening rash, acneiform	Skin and subcutaneous tissue disorders	medDRA	Systematic Assessment		EG0004 events3 affected50 at risk
Rash, generalized	Skin and subcutaneous tissue disorders	medDRA	Systematic Assessment		EG0003 events3 affected50 at risk
Depression	Psychiatric disorders	medDRA	Systematic Assessment		EG0003 events3 affected50 at risk
Worsening depression	Psychiatric disorders	medDRA	Systematic Assessment		EG0002 events2 affected50 at risk
Edema, limb	General disorders	medDRA	Systematic Assessment		EG00030 events23 affected50 at risk
Fatigue	General disorders	medDRA	Systematic Assessment		EG00014 events12 affected50 at risk
Worsening fatigue	General disorders	medDRA	Systematic Assessment		EG0003 events3 affected50 at risk
Blood creatinine increased	Renal and urinary disorders	medDRA	Systematic Assessment		EG0009 events8 affected50 at risk
Erythrocytosis	Blood and lymphatic system disorders	medDRA	Systematic Assessment	Post-transplant erythrocytosis	EG0008 events8 affected50 at risk
Pyrexia	General disorders	medDRA	Systematic Assessment		EG0009 events9 affected50 at risk
Dizziness	Nervous system disorders	medDRA	Systematic Assessment		EG0004 events4 affected50 at risk
Hyperglycemia	Metabolism and nutrition disorders	medDRA	Systematic Assessment		EG0004 events3 affected50 at risk
Mental concentration difficulty	Psychiatric disorders	medDRA	Systematic Assessment	Impairment or fogginess	EG0003 events3 affected50 at risk
Proteinuria	Renal and urinary disorders	medDRA	Systematic Assessment		EG00012 events11 affected50 at risk
Worsening proteinuria	Renal and urinary disorders	medDRA	Systematic Assessment		EG0008 events7 affected50 at risk
Chills	General disorders	medDRA	Systematic Assessment		EG0009 events7 affected50 at risk
Visual acuity reduced	Eye disorders	medDRA	Systematic Assessment		EG0004 events4 affected50 at risk
Generalized body aches	General disorders	medDRA	Systematic Assessment		EG0004 events4 affected50 at risk
Leukopenia	Blood and lymphatic system disorders	medDRA	Systematic Assessment		EG00012 events9 affected50 at risk
Worsening leukopenia	Blood and lymphatic system disorders	medDRA	Systematic Assessment		EG0003 events2 affected50 at risk
Hyponatremia	Renal and urinary disorders	medDRA	Systematic Assessment		EG0003 events3 affected50 at risk
Hypokalemia	Metabolism and nutrition disorders	medDRA	Systematic Assessment		EG0003 events2 affected50 at risk
Low back pain	Musculoskeletal and connective tissue disorders	medDRA	Systematic Assessment		EG0005 events4 affected50 at risk
Insomnia	Psychiatric disorders	medDRA	Systematic Assessment		EG0005 events5 affected50 at risk
Chest pain	Musculoskeletal and connective tissue disorders	medDRA	Systematic Assessment		EG0002 events2 affected50 at risk
Excessive thirst	Metabolism and nutrition disorders	medDRA	Systematic Assessment		EG0005 events3 affected50 at risk
Hematuria	Renal and urinary disorders	medDRA	Systematic Assessment		EG0007 events7 affected50 at risk
Flank pain	Musculoskeletal and connective tissue disorders	medDRA	Systematic Assessment		EG0002 events2 affected50 at risk
BK viremia	Investigations	medDRA	Systematic Assessment	> 500 copies post-transplant	EG0003 events3 affected50 at risk
Donor specific antibody positive	Immune system disorders	medDRA	Systematic Assessment	post-transplant	EG0002 events2 affected50 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	medDRA	Systematic Assessment		EG00010 events8 affected50 at risk
Rhinorrhea	Respiratory, thoracic and mediastinal disorders	medDRA	Systematic Assessment		EG0007 events6 affected50 at risk
Hypertension	Vascular disorders	medDRA	Systematic Assessment		EG00013 events10 affected50 at risk
Worsening hypertension	Vascular disorders	medDRA	Systematic Assessment		EG0009 events9 affected50 at risk
Headache	Nervous system disorders	medDRA	Systematic Assessment		EG00011 events8 affected50 at risk
Worsening headache	Nervous system disorders	medDRA	Systematic Assessment		EG0003 events3 affected50 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	medDRA	Systematic Assessment		EG0004 events4 affected50 at risk
Dyspnea exertional	Respiratory, thoracic and mediastinal disorders	medDRA	Systematic Assessment		EG0003 events3 affected50 at risk
Worsening dyspnea	Respiratory, thoracic and mediastinal disorders	medDRA	Systematic Assessment		EG0003 events3 affected50 at risk

ID	Term
D009421	Nervous System Malformations
D009422	Nervous System Diseases
D020271	Heredodegenerative Disorders, Nervous System
D019636	Neurodegenerative Diseases
D011115	Polyneuropathies
D010523	Peripheral Nervous System Diseases
D009468	Neuromuscular Diseases
D000013	Congenital Abnormalities
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D030342	Genetic Diseases, Inborn

ID	Term
D020123	Sirolimus
D018942	Macrolides
D007783	Lactones
D009930	Organic Chemicals